title: Dietary zinc supplementation of 3xTg-AD mice increases BDNF levels and prevents cognitive deficits as well as mitochondrial dysfunction.
abstract: The overall effect of brain zinc (Zn(2+)) in the progression and development of Alzheimer's disease (AD) is still not completely understood. Although an excess of Zn(2+) can exacerbate the pathological features of AD, a deficit of Zn(2+) intake has also been shown to increase the volume of amyloid plaques in AD transgenic mice. In this study, we investigated the effect of dietary Zn(2+) supplementation (30 p.p.m.) in a transgenic mouse model of AD, the 3xTg-AD, that expresses both β amyloid (Aβ)- and tau-dependent pathology. We found that Zn(2+) supplementation greatly delays hippocampal-dependent memory deficits and strongly reduces both Aβ and tau pathology in the hippocampus. We also evaluated signs of mitochondrial dysfunction and found that Zn(2+) supplementation prevents the age-dependent respiratory deficits we observed in untreated 3xTg-AD mice. Finally, we found that Zn(2+) supplementation greatly increases the levels of brain-derived neurotrophic factor (BDNF) of treated 3xTg-AD mice. In summary, our data support the idea that controlling the brain Zn(2+) homeostasis may be beneficial in the treatment of AD.
authors.affiliation: Molecular Neurology Unit-Center of Excellence on Aging, University 'G. d'Annunzio', Chieti-Pescara, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Corona
authors.forename: F
authors.initials: F
authors.lastname: Masciopinto
authors.forename: E
authors.initials: E
authors.lastname: Silvestri
authors.forename: A Del
authors.initials: AD
authors.lastname: Viscovo
authors.forename: R
authors.initials: R
authors.lastname: Lattanzio
authors.forename: R La
authors.initials: RL
authors.lastname: Sorda
authors.forename: D
authors.initials: D
authors.lastname: Ciavardelli
authors.forename: F
authors.initials: F
authors.lastname: Goglia
authors.forename: M
authors.initials: M
authors.lastname: Piantelli
authors.forename: L M T
authors.initials: LM
authors.lastname: Canzoniero
authors.forename: S L
authors.initials: SL
authors.lastname: Sensi
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D003072:Cognition Disorders / Q000517:prevention & control*; D019587:Dietary Supplements; D006624:Hippocampus / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000502:physiology*; D015032:Zinc / Q000008:administration & dosage / Q000627:therapeutic use*; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D019208:Brain-Derived Neurotrophic Factor; D016875:tau Proteins; D015032:Zinc